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  1. Article: Orientia tsutsugamushi

    Fisher, James / Gonzales, Casey / Chroust, Zachary / Liang, Yuejin / Soong, Lynn

    Pathogens (Basel, Switzerland)

    2022  Volume 12, Issue 1

    Abstract: ... Orientia ... ...

    Abstract Orientia tsutsugamushi
    Language English
    Publishing date 2022-12-29
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens12010053
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Differential cellular immune responses against Orientia tsutsugamushi Karp and Gilliam strains following acute infection in mice.

    Thiriot, Joseph D / Liang, Yuejin / Gonzales, Casey / Sun, Jiaren / Yu, Xiaoying / Soong, Lynn

    PLoS neglected tropical diseases

    2023  Volume 17, Issue 12, Page(s) e0011445

    Abstract: Scrub typhus is a leading cause of febrile illness in endemic countries due to infection with Orientia tsutsugamushi (Ot), a seriously understudied intracellular bacterium. Pulmonary involvement associated with vascular parasitism in patients is common ... ...

    Abstract Scrub typhus is a leading cause of febrile illness in endemic countries due to infection with Orientia tsutsugamushi (Ot), a seriously understudied intracellular bacterium. Pulmonary involvement associated with vascular parasitism in patients is common and can develop into life threatening interstitial pneumonia. The diverse antigenicity of Ot genotypes and inter-strain differences in genome content are connected to varied virulence and clinical outcomes; however, detailed studies of strain-related pulmonary immune responses in human patients or small animal models of infection are lacking. In this study, we have used two clinically prevalent bacterial strains (Karp and Gilliam) to reveal cellular immune responses in inflamed lungs and potential biomarkers of disease severity. The results demonstrate that outbred CD-1 mice are highly susceptible to both Karp and Gilliam strains; however, C57BL/6 (B6) mice were susceptible to Karp, but resistant to Gilliam (with self-limiting infection), corresponding to their tissue bacterial burdens and lung pathological changes. Multicolor flow cytometric analyses of perfused B6 mouse lungs revealed robust and sustained influx and activation of innate immune cells (macrophages, neutrophils, and NK cells), followed by CD4+ and CD8+ T cells, during Karp infection, but such responses were greatly attenuated during Gilliam infection. The robust cellular responses in Karp-infected B6 mice positively correlated with significantly early and high levels of serum cytokine/chemokine protein levels (CXCL1, CCL2/3/5, and G-CSF), as well as pulmonary gene expression (Cxcl1/2, Ccl2/3/4, and Ifng). In vitro infection of B6 mouse-derived primary macrophages also revealed bacterial strain-dependent immune gene expression profiles. This study provided the lines of evidence that highlighted differential tissue cellular responses against Karp vs. Gilliam infection, offering a framework for future investigation of Ot strain-related mechanisms of disease pathogenesis vs. infection control.
    MeSH term(s) Humans ; Mice ; Animals ; Orientia tsutsugamushi/genetics ; Mice, Inbred C57BL ; Scrub Typhus/epidemiology ; Antibodies ; Immunity, Cellular
    Chemical Substances Antibodies
    Language English
    Publishing date 2023-12-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0011445
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Alterations in germinal center formation and B cell activation during severe Orientia tsutsugamushi infection in mice.

    Gonzales, Casey / Liang, Yuejin / Fisher, James / Card, Galen / Sun, Jiaren / Soong, Lynn

    PLoS neglected tropical diseases

    2023  Volume 17, Issue 5, Page(s) e0011090

    Abstract: Scrub typhus is a poorly studied but life-threatening disease caused by the intracellular bacterium Orientia tsutsugamushi (Ot). Cellular and humoral immunity in Ot-infected patients is not long-lasting, waning as early as one-year post-infection; ... ...

    Abstract Scrub typhus is a poorly studied but life-threatening disease caused by the intracellular bacterium Orientia tsutsugamushi (Ot). Cellular and humoral immunity in Ot-infected patients is not long-lasting, waning as early as one-year post-infection; however, its underlying mechanisms remain unclear. To date, no studies have examined germinal center (GC) or B cell responses in Ot-infected humans or experimental animals. This study was aimed at evaluating humoral immune responses at acute stages of severe Ot infection and possible mechanisms underlying B cell dysfunction. Following inoculation with Ot Karp, a clinically dominant strain known to cause lethal infection in C57BL/6 mice, we measured antigen-specific antibody titers, revealing IgG2c as the dominant isotype induced by infection. Splenic GC responses were evaluated by immunohistology, co-staining for B cells (B220), T cells (CD3), and GCs (GL-7). Organized GCs were evident at day 4 post-infection (D4), but they were nearly absent at D8, accompanied by scattered T cells throughout splenic tissues. Flow cytometry revealed comparable numbers of GC B cells and T follicular helper (Tfh) cells at D4 and D8, indicating that GC collapse was not due to excessive death of these cell subtypes at D8. B cell RNAseq analysis revealed significant differences in expression of genes associated with B cell adhesion and co-stimulation at D8 versus D4. The significant downregulation of S1PR2 (a GC-specific adhesion gene) was most evident at D8, correlating with disrupted GC formation. Signaling pathway analysis uncovered downregulation of 71% of B cell activation genes at D8, suggesting attenuation of B cell activation during severe infection. This is the first study showing the disruption of B/T cell microenvironment and dysregulation of B cell responses during Ot infection, which may help understand the transient immunity associated with scrub typhus.
    MeSH term(s) Humans ; Mice ; Animals ; Scrub Typhus/microbiology ; Mice, Inbred C57BL ; Orientia tsutsugamushi ; T-Lymphocytes ; Germinal Center
    Language English
    Publishing date 2023-05-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0011090
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Brain transcriptomics reveal the activation of neuroinflammation pathways during acute

    Liang, Yuejin / Aditi / Onyoni, Florence / Wang, Hui / Gonzales, Casey / Sunyakumthorn, Piyanate / Wu, Ping / Samir, Parimal / Soong, Lynn

    Frontiers in immunology

    2023  Volume 14, Page(s) 1194881

    Abstract: Scrub typhus, an acute febrile illness caused ... ...

    Abstract Scrub typhus, an acute febrile illness caused by
    MeSH term(s) Animals ; Mice ; Scrub Typhus/genetics ; Neuroinflammatory Diseases ; Transcriptome ; Orientia tsutsugamushi/genetics ; Brain/pathology
    Language English
    Publishing date 2023-06-22
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1194881
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: CCR7/dendritic cell axis mediates early bacterial dissemination in

    Liang, Yuejin / Wang, Hui / Gonzales, Casey / Thiriot, Joseph / Sunyakumthorn, Piyanate / Melby, Peter C / Sun, Jiaren / Soong, Lynn

    Frontiers in immunology

    2022  Volume 13, Page(s) 1061031

    Abstract: Scrub typhus is a life-threatening zoonosis caused by the obligate intracellular ... ...

    Abstract Scrub typhus is a life-threatening zoonosis caused by the obligate intracellular bacterium
    MeSH term(s) Mice ; Animals ; Orientia tsutsugamushi ; Scrub Typhus ; Receptors, CCR7 ; Disease Models, Animal ; Dendritic Cells/pathology
    Chemical Substances Receptors, CCR7 ; Ccr7 protein, mouse
    Language English
    Publishing date 2022-12-22
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1061031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Distinct Role of TNFR1 and TNFR2 in Protective Immunity Against

    Liang, Yuejin / Fisher, James / Gonzales, Casey / Trent, Brandon / Card, Galen / Sun, Jiaren / Tumanov, Alexei V / Soong, Lynn

    Frontiers in immunology

    2022  Volume 13, Page(s) 867924

    Abstract: Infection ... ...

    Abstract Infection with
    MeSH term(s) Animals ; Mice ; Mice, Inbred C57BL ; Orientia tsutsugamushi ; Receptors, Tumor Necrosis Factor, Type I/immunology ; Receptors, Tumor Necrosis Factor, Type II/immunology ; Scrub Typhus/immunology
    Chemical Substances Receptors, Tumor Necrosis Factor, Type I ; Receptors, Tumor Necrosis Factor, Type II ; Tnfrsf1a protein, mouse ; Tnfrsf1b protein, mouse
    Language English
    Publishing date 2022-04-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.867924
    Database MEDical Literature Analysis and Retrieval System OnLINE

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